RESEARCH BRIEF

Lactate Clearance as a Marker of Mortality in PediatricIntensive Care Unit
A MUNDE, N KUMAR, RS BERI AND JM PULIYEL
From Department of Pediatrics, St. Stephens Hospital, Tis-Hazari, Delhi, India.
Correspondence to:
Dr Nirmal Kumar,
4, Rajpur Road, Qtr. B-2, Tis-Hazari,
Delhi 110 054, India.
nsk9_2000@yahoo.com
Received: January 15, 2014;
Initial review: January 20, 2014;
Accepted: May 13, 2014.

Objectives: To correlate lactate clearance with Pediatric Intensive Care Unit (PICU)
mortality. Methods: 45 (mean age 40.15 mo, 60% males) consecutive admissions in thePICU were enrolled between May 2012 to June 2013. Lactate clearance (Lactate level atadmission – level 6 hr later x 100 / lactate level at admission) in first 6 hours of hospitalization
was correlated to in-hospital mortality and PRISM score. Results: Twelve out of 45 patientsdied. 90% died among those with delayed/poor clearance (clearance <30%) compared to8.5% in those with good clearance (clearance >30%) (P<0.001). Lactate clearance <30%
predicted mortality with sensitivity of 75%, specificity of 97%, positive predictive value of90%, and negative predictive value of 91.42%. Predictability was comparable to PRISM
score >30. Conclusion: Lactate clearance at six hours correlates with mortality in the PICU.
Keywords: In-hospital mortality, Lactate clearance, PRISM score.

Hyperlactatemia is an indicator of inadequate
tissue perfusion, particularly in sepsis [1]. It
reflects severity of illness with significant
prognostic implications [2]. The severity andduration of lactic acidosis in critically ill patients
correlates with overall oxygen debt, and increased
production [3,4]. However, a single lactate measurement
has not been correlated to mortality consistently [5].

ABL 555 blood gas analyzer.
Lactate levels were estimated at admission and after
six hours of admission and the clearance was calculated
as follows: Lactate clearance = [Initial Lactate - CurrentLactate) × 100 / Initial Lactate].
A positive value denotes clearance of lactate, whereasa negative value denotes an increase in lactate afterintervention. Routine ICU care and investigations wereperformed and Pediatric Risk of Mortality (PRISM)
score was calculated. In-hospital mortality was theprimary outcome of interest.

Lactate clearance is the rate of fall in lactate after
resuscitation is started. This has shown more promise inpredicting mortality. Two studies in adult patients withshock showed that lactate clearance of <10% was related
to mortality [5,6]. There are no pediatric studies looking
at lactate clearance and mortality although Hatheril, et al.
[7] showed that persistent hyper-lactatemia at 24 hours(>2 mmol/dL) was associated with mortality. We
investigated whether lactate clearance in the early periodof resuscitation (first 6 hours of hospitalization) could
help predict mortality in pediatric patients.

Survivors and non-survivors were compared by theMann-Whitney test for continuous variables and by
Fisher’s exact test for categorical variables. For nonparametric data, pair-wise comparisons were made using
Wilcoxon’s signed-rank test. For continuous variable, weused t-test. A P value <0.05 was taken as statisticallysignificant. SPSS version 16.0 was used.

METHODSRESULTS

Admissions to the PICU (aged >1 month and <13 years)
were studied between May 2012 and June 2013 after
obtaining informed written consent from parents.
Children with inborn error of metabolism and trauma
were excluded. The study was approved by the hospitalethics committee. As a pilot study, a convenience sample
of 45 patients admitted consecutively was enrolled.
Heparinized syringe was used to collect venous blood.
Lactate estimation was done by Radiometer Copenhagen

Out of 45 children (mean age 40.15, range 1-144 months,
M:F ratio 1.5:1), twelve died. The initial lactate was not
significantly different between those who died and those
who survived [8.44 (3.27) vs 7.29 (3.31), P=0.18], butclearance at 6 hours was significantly lower in those whodied (-4.01%) than those who survived (55.53)(P<0.001). The mean (SD) PRISM score was also higher
in those who died compared with those who survived[43.6 (7.27) vs. 21.7 (9.2), P<0.001].

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MUNDE, et al.

LACTATE CLEARANCE IN PEDIATRIC INTENSIVETABLE I CORRELATION OF PRISM SCORE WITH LACTATE
CLEARANCE IN RELATION TO OBSERVED AND EXPECTEDMORTALITYWhere lactate clearance was <30% at 6 hours, nineout of ten died. In those with clearance >30% only threeout of thirty-five died. ROC curve analysis for mortality
prediction was 0.97 (P< 0.001) (Fig. 1). Three children
died within 24 hours. Mean (SD) duration of hospital stayin those with lactate clearance >30% was 18.5 (8.44) d(range 3-40), against 3.1 (2.61) d (range 1-9) in thosewith clearance <30%.
An inverse relationship was observed between lactate
clearance and PRISM score (Table I). Lactate clearance<30% at six hours predicted mortality with sensitivity of75%, specificity of 97%, PPV 90%, NPV 91.42%.
Observed and expected mortality was almost similar in
those having PRISM score of >30.
DISCUSSION
Lactate clearance at 6 hours was significantly associatedwith mortality as was a PRISM score >35. The ROC
curve shows mortality prediction of lactate clearance was0.977.

PRISM
score

Number ofpatients

Lactateclearance at
6 hrs (%)

Observedmortality(%)

Expected
mortality
(%)

01-05

0––

09

06-10

4

60.9

–

15

11-15

551.0

–

23

16-20

654.4

–3521-25

961.3–

49

26-30

348.0–

63

31-35

642.3

33.3

75

>35

120.7

83.3

>75

Studies have suggested the value of monitoring for lactate
clearance with hypo-perfusion [6,7]. One of these studies
found a 41% higher mortality rate among those subjects
who failed to reach a lactate clearance of 10% whencompared with those that effectively cleared lactate (60%vs. 19% mortality) during the early resuscitative period.
The only study in pediatric age group conducted byHatheril, et al. [7], showed that persistent hyper-lactatemia>2 mmol/L after 24 hours was associated with 93%
mortality, as compared to 30% in those children whoselactate level had normalized. Following the study in adults,
we used lactate clearance at 6 hours [6]. We found that wecan predict mortality as early as 6 hours. In our study PPV,NPV and ROC curve analysis for mortality prediction at 6hours of lactate clearance are comparable to Hatheril, et al.
[7] findings at 24 hours.

The duration of stay was longer in those with goodclearance because of early mortality in the ones with poorclearance. There were very few survivors among thosewith poor clearance to allow us to compare duration ofstay in survivors in the two groups.
High admission lactate was a significant independent
predictor of mortality in adult patients admitted to ICU[8-10] but it could not be replicated in other studies [6,11].

We found that a lactate clearance ≤30% at six hours
and PRISM score more than 30 have high prediction formortality. Lactate clearance can probably be used as ascreening tool to predict adverse outcome. We haveprovided stratification and cut-off values of lactate
clearance which need validation by more studies withlarger samples.
Acknowledgement: Dr DK Shukla for data analysis.
Contributors: AM: Design, Manuscript writing, Data-Collection
and Data Interpretation; NK: Concept, Design, Manuscript
drafting and guarantor of the study; RSB: Manuscript writing
and JMP: Manuscript Drafting and Design of the study.
Funding: None; Competing interest: None stated.

REFERENCES
Area under curve = 0.97%

1. Weil MH, Afifi AA. Experimental and clinical studies onlactate and pyruvate as indicators of the severity of acutecirculatory failure (shock). Circulation. 1970;41:989-1001.

FIG. 1 ROC curve for lactate clearance at 6 hours in relation tomortality prediction.

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LACTATE CLEARANCE IN PEDIATRIC INTENSIVE
WHAT THIS STUDY ADDS?

• Lactate Clearance <30% at 6 hours of admission predicts mortality in PICU admitted patients.
• Lactate clearance < 30% at 6 hours correlates well with PRISM score for mortality prediction.

7. Hatherill M, McIntyre AG, Wattie M, Dellofer P, Murdoch
IA. Early hyperlactatemia in critically ill children.
Intensive Care Med. 2000;26:314-8.
8. Khosravani H, Shahpori R, Stelfox HT, Kirkpatrich AW,Laupland KB. Occurrence and adverse effect on outcomeof hyperlactatemia in the critically ill. Critical Care.
2009;13:R90.
9. Smith I, Kumar P, Molloy S, Rhodes A, Newman PJ,
Groundi RM, et al. Base excess and lactate as prognostic
indicators for patients admitted to intensive care. Intensive
Care Med. 2001;27:74-83.
10. Jansen TC, Bommel JV, Schoonderbeek FJ, Sleeswijk
visser SJ, Klooster JM, Lima AP, et al. Early lactate-guidedtherapy in intensive care unit patients: a multicenter, openlabel, randomized controlled trial. Am J Respir Crit CareMed. 2010;182:752-61.
11. Del Portal DA, Shofer F, Mikkelsen ME, Dorsey PJ,
Gaieski DF, Synnestvedt M, et al. Emergency department
lactate is associated with mortality in older adults admittedwith and without infections. Acad Emerg Med.
2010;17:260-8.

2. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM,Knaus WA, et al. Definitions for sepsis and organ failureand guidelines for the use of innovative therapies in sepsis– The ACCP / SCCM Consensus Conference Committee.
Chest. 1992;101:1644-55.
3. Bakker J, Gris P, Coffernils M, Kahn RJ, Vincent JL. Serial
blood lactate levels can predict the development of multiple
organ failure following septic shock. Am J Surg. 1996;
171:221-6.
4. Bernardin G, Pradler C, Tiger F, Deloffre P, Mattei M.
Blood pressure and arterial lactate level are early indicatorsof short-term survival in human septic shock. Intensive
Care Med. 1996;22:17-25.
5. Arnold RC, Shapiro NI, Jones AE, Schorr C, Pope J,Casner E, et al. Multi-center study of early lactate clearance
as a determinant of survival in patients with presumedsepsis. Shock. 2009;34:36-40.
6. Nguyen HB, Rivers EP, Knoblich BP, Jacobsen G, Muzzin
A, Ressler JA, et al. Early lactate clearance is associatedwith improved outcome in severe sepsis and septic shock.
Crit Care Med. 2004;32:1637-42.

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